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CAS No. : | 5394-63-8 | MDL No. : | MFCD00040468 |
Formula : | C7H10O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | XFRBXZCBOYNMJP-UHFFFAOYSA-N |
M.W : | 142.15 | Pubchem ID : | 79368 |
Synonyms : |
|
Num. heavy atoms : | 10 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.57 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 35.58 |
TPSA : | 35.53 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.32 cm/s |
Log Po/w (iLOGP) : | 1.95 |
Log Po/w (XLOGP3) : | 1.19 |
Log Po/w (WLOGP) : | 1.2 |
Log Po/w (MLOGP) : | 0.65 |
Log Po/w (SILICOS-IT) : | 1.4 |
Consensus Log Po/w : | 1.28 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -1.47 |
Solubility : | 4.81 mg/ml ; 0.0338 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.53 |
Solubility : | 4.17 mg/ml ; 0.0294 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.24 |
Solubility : | 8.27 mg/ml ; 0.0582 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 3.18 |
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P501-P260-P202-P240-P210-P233-P201-P243-P241-P242-P264-P280-P370+P378-P308+P313-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235-P405 | UN#: | 1993 |
Hazard Statements: | H315-H319-H361-H373-H225 | Packing Group: | Ⅱ |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In xylene for 2h; Heating; also with other heterocyclic amines, azido-, and chloroacetamide; also in 2-methoxyethyl ether by heating in a microwave oven 4 times for 20 s; | |
96% | In xylene for 2h; Heating; also in 2-methoxyethyl ether by heating in a microwave oven 4 times for 20 s with cooling intervals; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In xylene for 0.5h; Heating; | |
59% | In xylene for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | In xylene for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In xylene at 120℃; for 1.5h; | |
at 120℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | for 0.0166667h; microwave irradiation; | |
79% | In xylene at 140℃; for 1.5h; | |
79% | With sodium acetate In tetrahydrofuran for 24h; Reflux; |
65% | In toluene at 180℃; for 0.166667h; Microwave irradiation; | |
In N,N-dimethyl-formamide at 125℃; Microwave irradiation; | ||
at 150℃; for 0.5h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In xylene for 0.5h; Heating; | |
85% | In xylene for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 5% 2: 36% | at 120 - 130℃; for 0.5h; Heating; | |
1: 18% 2: 18% | In xylene for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | ||
80% | In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 2h; | |
In xylene for 1h; Heating; |
In xylene at 150℃; for 0.5h; | ||
In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 6h; | 5.1.3. General procedure for preparation of acetoacetic esters derivatives (6a-d) General procedure: A solution of the appropriate alcohol, 5a-d, (25 mmol) and TMD (3.5 g, 25 mmol) in 10 ml xylene was heated under reflux in an oil bathat 150 °C, for 6 h. The reaction mixture was cooled and then xylene wasremoved under reduced pressure to yield products, 6a-d which were ina high level of purity and were used immediately in subsequent reactions.34 6a, a yellow oil, with bp 183-185 °C, (Lit. bp 185-187 °C), 6b, ayellow oil, with bp 200-201 °C, (Lit. bp 204-205 °C), 6c, a yellow oil,with bp 115-117 °C, (Lit bp 120-122 °C) and 6d, a yellow oil, with bp270-271 °C, (Lit bp 275-276 °C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In xylene at 150℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | In xylene for 1.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 2h; | |
80% | In toluene at 90℃; for 15h; | Benzyl 3-oxobutanoate (4e). A mixture of 1.31 g (9.2 mmol) of 2,2,6-trimethyl-4H-1,3-dioxin-4-one and 1 g (9.2 mmol) of benzyl alcohol in 7 mL of toluene was stirred for 15 h at 90°C. When the reaction was complete (TLC, ethyl acetate-hexane, 7 : 1), the solvent was distilled off, and the residue (yellow liquid) was purified by flash chromatography on silica gel using chloroform-diethyl ether (1 : 1) as eluent; the product was dried in air. Yield 80%, yellow liquid. The spectral parameters of compound 4e were consistent with those given in [13]. |
69% | at 140℃; for 2h; |
65% | In 5,5-dimethyl-1,3-cyclohexadiene Reflux; | |
In toluene for 20h; Reflux; | ||
In 5,5-dimethyl-1,3-cyclohexadiene Reflux; | ||
In 5,5-dimethyl-1,3-cyclohexadiene at 150℃; for 6h; | 5.1.3. General procedure for preparation of acetoacetic esters derivatives (6a-d) General procedure: A solution of the appropriate alcohol, 5a-d, (25 mmol) and TMD (3.5 g, 25 mmol) in 10 ml xylene was heated under reflux in an oil bathat 150 °C, for 6 h. The reaction mixture was cooled and then xylene wasremoved under reduced pressure to yield products, 6a-d which were ina high level of purity and were used immediately in subsequent reactions.34 6a, a yellow oil, with bp 183-185 °C, (Lit. bp 185-187 °C), 6b, ayellow oil, with bp 200-201 °C, (Lit. bp 204-205 °C), 6c, a yellow oil,with bp 115-117 °C, (Lit bp 120-122 °C) and 6d, a yellow oil, with bp270-271 °C, (Lit bp 275-276 °C). | |
In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.3% | In o-xylene at 141℃; for 2h; | 1.1 Step 1) 2-cyanoethyl acetoacetate 2,2,6-Trimethyl-4H-1,3-dioxan-4-one (15.50 g, 109.0 mmol), 3-hydroxypropionitrile (7.75 g, 109 mmol) and o-xylene (20 mL)The reaction was carried out at 141 ° C for 2 hours. Cool to room temperature,The solvent was evaporated to give a pale yellow oil (16.63 g, 98.30%). |
90% | In 5,5-dimethyl-1,3-cyclohexadiene at 140 - 145℃; for 1h; | 29 That is accurately weighed 1.42g 10mmol of 2,2,6-trimethyl-1,3-dioxin-4-one -4H and 0.82mL Approximately 12mmol of 2-hydroxy-acetonitrile, dissolved in 10mL of ethylene and heated to 140-145 ° C, The reaction was refluxed for 1h, cooled to room temperature, the solvent was removed by rotary evaporation and the residue was purified by flash column chromatography pure Of Compound S711.4g, 90% yield. |
81.6% | In xylene at 140 - 145℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In toluene at 20℃; for 12.25h; Reflux; | |
90% | for 0.0333333h; microwave irradiation; | |
In N,N-dimethyl-formamide at 125℃; Microwave irradiation; |
In toluene at 165℃; for 0.166667h; Microwave irradiation; | ||
In toluene for 3h; Reflux; | ||
In toluene for 3h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 2,2,6-trimethyl-4H-1,3-dioxin-4-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1.75h; Stage #2: 1-benzoyl-1H-benzotriazole In tetrahydrofuran at -78 - 20℃; | |
65% | Stage #1: 2,2,6-trimethyl-4H-1,3-dioxin-4-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 1.5h; Inert atmosphere; Stage #2: 1-benzoyl-1H-benzotriazole In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In xylene; at 120℃; for 0.5h; | To a solution of 1.52 g of <strong>[14667-47-1]methyl 2-aminonicotinate</strong> in 3 ml of xylene was added 1.3 ml of 2,2,6-trimethyl-4H-1,3-dioxin-4-one, and the mixture was heated at 120C for 30 minutes. The reaction solution was subjected to silica gel column chromatography to obtain 1.15 g of methyl 2-(3-oxobutyrylamino)nicotinate [Compound No. (1B-1)] as a white solid. 1H-NMR (270MHz,DMSO-d6) delta (ppm): 2.22 (s, 3H), 3.68 (s, 2H), 3.74 (s, 3H), 7.27~7.32 (m, 1H), 8.10~8.20 (m, 1H), 8.49~8.51 (m, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 5h; Dean-Stark; Inert atmosphere; | |
In m-xylene at 120 - 150℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In toluene at 20℃; for 12.25h; Reflux; | |
91% | In toluene at 150℃; for 6h; | General procedure d General procedure: To a solution of 2,2,6-trimethyl-4H-1,3-dioxin-4-one (1 eq) in toluene (5 M) at room temperature, the corresponding alcohol or amine (1 eq) was added. The mixture was heated at 150 °C for 6 hours, then allowed to cool to room temperature and concentrated in vacuum. The remaining residue was purified by flash column chromatography on silica gel using ethyl acetate/hexane as eluent to afford the dicarbonyl compound. The following dicarbonyl compounds were synthesized following General procedure d. |
In m-xylene at 120 - 150℃; |
In 5,5-dimethyl-1,3-cyclohexadiene Reflux; | ||
In 5,5-dimethyl-1,3-cyclohexadiene for 6h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | In toluene; for 16h;Heating / reflux; | Step 1 : Preparation of 5-NITRO-2- (3-OXO-BUTYRYLAMINO)-BENZOIC acid methyl ester :; To a suspension of 4-nitro methyl anthranilate (25. 6 mmol, 5G) in toluene (60ML) was added 2, 2, 6-trimethyl-1, 3-dioxin-4-one (28. 2 mmol, 3. 78ML). The solution was refluxed for 16 hours and left to stand at RT for lhour, the formed precipitate was successively filtered, washed with toluene and dried to afford 5- NITRO-2- (3-OXO-BUTYRYLAMINO)-BENZOIC acid methyl ester as a yellow solid (5. 61g, 78%). H NMR (400 MHz, DMSO-D6) 8 appear as mixture of tautomers, enol form not described, 11. 06 (s, 1H, BROAD) ; 8. 66 (d, 1H, J=2. 74) ; 8. 50 (d, 1H, J=9. 3) ; 8. 46 (dd, 1H, J=9. 3, 2. 7) ; 3. 93 (s, 3H) ; 3. 802 (S,No.2H) ; 2. 24 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In 5,5-dimethyl-1,3-cyclohexadiene Heating; | |
8 g | In 5,5-dimethyl-1,3-cyclohexadiene at 110 - 140℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 1 - Synthesis of crude 5-methoxycarbonyl-4-(2,3-dichlorophenyl)-2,6- dimethyl-1 ,4-dihydropyridine-3-carboxylic acid[0020] The starting materials 2,2,6-trimethyl-4/-/-1 ,3-dioxin-4-one (89.2g, 0.63 mol) and 3-hydroxypropionitrile (44.6g, 0.63 mol) were heated in an oil bath at 120C for 3h, during which acetone (the reaction byproduct) was distilled off. The reaction mixture was cooled to room temperature, and isopropanol (570ml_), methyl 3-aminocrotonate (65.7g, 0.57 mol) and 2,3-dichlorobenzaldehyde (100.0g, 0.57 mol) were added. The reaction mixture was heated to reflux, and some of the isopropanol (340m L) was distilled off. The reaction mixture was then cooled in an ice-water bath and dichloromethane (230m L) and a solution of NaOH (28.7g, 0.72 mol) in water (290ml_) were added. After stirring at room temperature for several hours, the reaction mixture was diluted with water and the layers were separated. The aqueous phase was extracted once more with dichloromethane, after which it was cooled in an ice-water bath and phosphoric acid (85%, 25ml_) was added. After precipitation and stirring, the solids were collected by filtration and washed with water. Drying under high vacuum at 40C gave carboxylic acid 2 as a yellow powder (126 g, 62% yield). Analysis by HPLC indicates a purity of 89.23%, with 3.17% of diacid 5 present. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In toluene at 110℃; for 0.416667h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Sodium hydroxide (1.06 g, 26. 5 mmol) was added to a solution of <strong>[24835-08-3]2-nitrobenzylamine hydrochloride</strong> (5.0 g, 26.5 mmol) in a mixed solvent comprising 20 ml of methanol and 2 ml of water, followed by stirring at room temperature for 30 minutes. Then, the reaction solution was concentrated under reduced pressure, toluene was added to the resulting residue, followed by azeotropic water separation under reduced pressure to distill the solvent off. To the resulting residue, 100 ml of m-xylene and 2,2,6-trimethyl-1,3-dioxin-4-one (3.77 g, 26.5 mmol) were added, followed by reflux under heating with stirring for 1 hour with azeotropic water separation with a dean-stark apparatus. After the reaction, ethyl acetate and water were added, and the organic layer was separated, dried with saturated aqueous sodium chloride and over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=9/1 to 1/1) to obtain 2.27 g of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; benzotriazol-1-ol; trifluoroacetic acid; In 1,2-dimethoxyethane; dichloromethane; | Example 35 3-(((3S,6S,10aS)-6-((S)-2-(methylamino)propanamido)-5-oxodecahydropyrrolo[1,2-a]azocine-3-carboxamido)methyl)benzyl 3-oxobutanoate: The title compound was prepared according to the steps and intermediates as described below. To <strong>[34231-22-6](3-(aminomethyl)phenyl)methanol</strong> (10 mg) in dry dichloromethane (1 mL) were added 1j (13.7 mg), EDC.HCl (7 mg), HOBt (5.0 mg), N-methylmorpholine (10 mul) and the resulting mixture was purified using semi-prep HPLC (TFA modifier). To a mixture of the isolated product (5 mg), 2,2,4-trimethyl-6-keto-1,3-dioxin (10 mul) in dimethoxyethane (1 mL) was stirred overnight at 80 C. The mixture was concentrated and diluted with dichloromethane (1 mL). Trifluoroacetic acid (0.3 mL) was added to the reaction mixture and stirred 10 min at rt. The reaction mixture was concentrated and the residue was purified using semi-prep HPLC (TFA modifier) to give a white solid as TFA salt. LCMS: m/e 515.2 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium acetate at 130℃; for 0.333333h; Microwave irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium acetate at 130℃; for 0.333333h; Microwave irradiation; | 6.2 General procedure (Method A) for the synthesis of intermediate acetoacetates 2-5 General procedure: 2,2,6-trimethyl-4H-1,3-dioxin-4-one (1.0 mL, 7.7 mmol) and alcohol (5.9 mmol) were mixed with potassium acetate (241 mg, 2.9 mmol) in a microwave vial. The mixture was microwaved for 20 min at 130 °C and the resulting mixture was chromatographed on silica gel (cHex/EtOAc 100/0-70/30). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | In 5,5-dimethyl-1,3-cyclohexadiene at 130℃; for 2h; | |
24 g | In 5,5-dimethyl-1,3-cyclohexadiene at 130℃; for 2h; | 59.59B Methyl 3-(N-benzyl-3-oxobutanamido) propanoate To a solution of 59A (20 g, 0.103 mmol) in xylenes (250 mL) was slowly added 2, 2, 6-trimethyl-4H-l, 3- dioxin-4-one (16.2 mL, 235.3 mmol) and the reaction was stirred at 130 °C for 2 h. The reaction was then concentrated and the crude material was cooled and washed with cold petroleum ether to give 24 g of 59B as brown oil. 1H NMR (400 MHz, CDC13) δ 7.15- 7.39 (5 H, m), 4.50 (2 H, s), 3.70 (3 H, s), 3.40-3.60 (2 H, m), 2.70 (2 H, s), 2.30-2.50 (2 H, m), 2.20 (3 H, s) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | In 5,5-dimethyl-1,3-cyclohexadiene; for 4h;Reflux; Inert atmosphere; | To a solution of Boc-amino acetone3 17 (4.21 g, 24.3 mmol) in xylenes (24 mL) was added 2,2,6-trimethyl-4H-1,3-dioxin-4-one 18 (7.1 mL, 48.6 mmol). The reaction was heated to reflux (130 C) for 4 h, was cooled to 23 C and concentrated under reduced pressure to afford crude beta-ketoamide. Purification by flash column chromatography (CH2Cl2:Et2O 90:10) provided mixed fractions of beta-ketoamide and alpha,beta-unsaturated lactam 19. alpha,beta-Unsaturated lactam 19 was isolated (1.37, 24%) as a yellow oil. The mixed fractions were re-subjected to flash column chromatography (CH2Cl2:Et2O 90:10) which provided alpha,beta-unsaturated lactam 19 (1.78 g, 31%) for a combined yield of 3.15 g (55%) of a yellow oil. To a solution of alpha,beta-unsaturated lactam 19 (1.40 g, 6.0 mmol) in toluene (120 mL) was added DIBAL-H in hexanes (12 mL, 1.0 M solution, 12 mmol) at -78 C. The reaction was stirred for 4 h, quenched with EtOAc (10 mL)and Rochelle?s salt (20 mL) at -78 C, and allowed to warm to 23 C while stirring vigorously overnight. The solution was diluted with CH2Cl2 (300 mL) and poured over Celite. The organic extracts were separated and washed with brine (60 mL), dried over Na2SO4, decanted, and concentrated under reduced pressure. Purification by flash column chromatography (hexanes:EtOAc 40:60) delivered allylic alcohol (408 mg, 28%) as an orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42 mg | In toluene at 150℃; for 0.0833333h; Irradiation; Inert atmosphere; | 4.1.2.1 9,10-Dimethoxy-2-methyl-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-4-one (1b) 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.065mL, 0.48mmol) was added to a stirred solution of imine 1a (50mg, 0.24mmol) dissolved in dry toluene (0.5mL). The mixture was irradiated at 150°C, 300W, for 5minand then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-MeOH, 98:2) gave 1b (42mg, 70%) as a white powder. Characterization data were in agreement with published data [33,31]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43 mg | With triethylamine In toluene for 3h; Reflux; Inert atmosphere; | 4.1.3.1 9,10-Dimethoxy-2,11b-dimethyl-7,11b-dihydro-4H,6H- [1,3]oxazino[2,3-a]isoquinolin-4-one (1c) 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (0.06mL, 0.44mmol) was added to a stirred solution of imine 1a (46mg, 0.22mmol) dissolved in dry toluene (5mL). Et3N (0.06mL, 0.44mmol) was added and the heated mixture was refluxed for 3h and then cooled to room temperature. The resulting solution was diluted with CH2Cl2 and washed with saturated aq. NaHCO3, water and brine. The combined organic extracts were dried with Na2SO4, filtered and concentrated. Purification by column chromatography (CH2Cl2-AcOEt, 60:40) gave 1c (43mg, 68%). IR (cm-1): 2932, 1662, 1515, 1409; 1H NMR (500MHz, CDCl3): δ=6.99 (s, 1H, H-8), 6.96 (s, 1H, H-11), 5.26 (s, 1H, H-3), 4.62 (ddd, J=12.7, 5.1, 2.7Hz; 1H, H-6α), 3.91 (s, 3H, OCH3-9), 3.66 (s, 3H, OCH3-10), 3.01 (m, 1H, H-6β), 2.91 (m, 1H, H-7α), 2.66 (m, 1H, H-7β), 1.97 (CH3-2), 1.81 (CH3-11b); 13C NMR (125MHz, CDCl3): δ=163.4 (CO), 162.1 (C-2), 149.2 (C-10), 148.8 (C-9), 128.5 (C-11a), 126.9 (C-7a), 110.7 (CH-8), 108.8 (CH-11), 98.4 (CH-3), 90.3 (C-11b), 56.1 (OCH3-10), 55.8 (OCH3-9), 35.9 (CH2-6), 27.6 (CH2-7), 23.1 (CH3-11b), 19.8 (CH3-2); ESMS m/z (%) 290 [M+H]+ (100) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In water for 2.5h; Reflux; Green chemistry; | |
With sodium acetate In tetrahydrofuran for 24h; Reflux; | ||
With sodium acetate In tetrahydrofuran for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.46 g | With sodium acetate In tetrahydrofuran Reflux; | 13.A A) N-(3-methylbutan-2-yl)-3-oxobutanamide To a mixture of 3-methylbutan-2-amine (1.00 g), 2,2,6-trimethyl-4H-1,3-didioxin-4-one (2.12 g) and tetrahydrofuran (3.0 mL) was added sodium acetate (941 mg) at room temperature. The reaction mixture was refluxed overnight, and cooled to room temperature. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (1.46 g). 1H NMR (400 MHz, CDCl3) δ 0.90 (6H, dd, J = 6.8, 4.0 Hz), 1.09 (3H, d, J = 6.8 Hz), 1.67-1.76 (1H, m), 2.27 (3H, s), 3.41 (2H, s), 3.83-3.92 (1H, m), 6.82 (1H,brs) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | In 5,5-dimethyl-1,3-cyclohexadiene at 120℃; for 5h; Dean-Stark; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | at 120℃; for 4h; | 1.1 Step 1) (R)-1-ethoxy-1-oxopropan-2-yl 3-oxobutanoate Step 1) (R)-1-ethoxy-1-oxopropan-2-yl 3-oxobutanoateA flask was charged with (D)-ethyl 2-hydroxypropanoate (11.8 g, 10 mmol)and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (14.2 g, 10 mmol) in turn, and then equipped with distillation apparatus or water segregator. The mixture was stirred at 120 °C for 4 hours. After the reaction, the mixture was cooled and concentrated to obtain the title compoundas puce liquid (12.9 g, 64%). MS(ESI, pos.ion) m/z: 203.1 [M+H]+; |
at 120℃; for 4h; | 1-1a Step 1-1a A solution of ethyl (R)-2-hydroxypropanoate (5 g, 42.3 mmol) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (6 g, 42.3 mmol) was stirred for 4 hours at 120° C. The mixture was concentrated under vacuum to give desired product (9 g, crude) as yellow oil, which was used in the next step without further purification. ESI MS m/z=203.25 [M+H]+. | |
at 120℃; for 4h; | Step 1-1a. A solution of ethyl (R)-2-hydroxypropanoate (5 g, 42.3 mmol) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (6 g, 42.3 mmol) was stirred for 4 hours at 120° C. The mixture was concentrated under vacuum to give desired product (9 g, crude) as yellow oil, which was used in the next step without further purification. ESI MS m/z=203.25 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | In para-xylene; at 150℃; for 4h;Inert atmosphere; | From Boc-aminoacetone 42: To a solution of Boc-aminoacetone 42(4.21 g, 24.3 mmol) in p-xylene (24 mL) was added dioxinone 43 (7.1mL, 48.6 mmol). The reaction was heated to reflux (150 C) for 4 h,cooled to 23 C, and concentrated under reduced pressure to afford the crude beta-keto amide. Purification by flash column chromatography (CH2Cl2-Et2O, 90:10) provided mixed fractions of beta-keto amideand unsaturated Boc-lactam 40. Unsaturated Boc-lactam 40was isolated (1.37 g, 24%) as a yellow oil. The mixed fractions were re-introduced to flash column chromatography (CH2Cl2-Et2O, 90:10), whichprovided an additional amount of lactam 40(1.78 g, 31%) as a yellow oil; combined total yield: 3.15 g (55%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 0.166667h;Inert atmosphere; | To a round-bottomed flask was added 42 (10.6 g, 61.0 mmol), dioxinone 43 (8.9 mL, 61.0 mmol), and xylenes (61 mL), and heated to 150 C for 10 min. The reaction was allowed to cool and the mixture was concentrated under reduced pressure to give beta-keto amide 41 as a brown solid; yield: 15.54 g (60.4 mmol, 99%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | In 5,5-dimethyl-1,3-cyclohexadiene for 3h; Reflux; | 100.1 Step-1: 3-acetyl-1,5-naphthyridin-2(1H)-one The mixture of 3-aminopicolinaldehyde (1 g, 8.19 mmol), and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (1.746 g, 12.28 mmol) in Xylene (30 ml) was heated to reflux for 3 hours, cooled to RT, filtered and washed with xylene twice to afford 3-acetyl-1,5-naphthyridin-2(1H)-one (1 g, 65%). 1H NMR (300 MHz, DMSO-d6) δ ppm 8.44-8.60 (m, 1H), 8.25 (s, 1H), 7.70 (d, J=1.47 Hz, 1H), 7.59 (dd, J=8.50, 4.40 Hz, 1H), 2.60 (s, 3H). LCMS (Method 1): Rt 1.05 min, m/z 189.10 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2h; Inert atmosphere; | |
86% | In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2h; Inert atmosphere; | |
56% | In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Reflux; | General procedure: Preparation of acetoacetamide derivatives (3a-e) was carried out as shown in Scheme 1. 2,2,6-Trimethyl-1,3- dioxine-4-one (1) (2eq) and appropriate arylamine (2a-e) (1eq) were mixed and refluxed for about 2-4h in toluene. The progress of the reactions was checked by TLC. Upon completion of the reaction, the product was filtered, washed with small portions of petroleum ether. Further purification was performed by crystallization of obtained product in hot ethanol. Characteristics data for prepared N-(aryl)-3- oxobutanamides are as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In decalin; for 12h;Reflux; | General procedure: To a solution of 2-aryloyl-phenol (1.00 equiv.) in trans-decalin (1.00 mL) was added2,2,6-trimethyl-1,3-dioxin-4-one (10.0 equiv) at room temperature. After being stirred at the reflux temperature for 12 h, the reaction mixture was concentrated in vacuo. The residue was purified by columnchromatography on silica gel to give coumarin analog. 3-Acetyl-7-methoxy-4-phenylcoumarin (4); 1H NMR (500 MHz, CDCl3) delta 7.51-7.48 (m, 3H), 7.29-7.26 (m, 2H), 7.10 (d, J = 8.7 Hz, 1H), 6.87 (s,1H), 6.76 (d, J = 8.8 Hz), 3.89 (s, 3H), 2.26 (s, 3H); 13C NMR (125 MHz, CDCl3) delta 199.5, 163.7, 155.5,152.9, 129.6, 129.5, 128.9, 128.5, 113.1, 113.0, 100.8, 56.0, 31.5; IR (neat): 2941, 2844, 1715, 1614,1550, 1509, 1492, 1463, 1444, 1372, 1295, 1285, 1263, 1204, 1166, 1135, 1117, 1077, 1044, 1025, 996,964, 839, 776, 753, 703, 655, 622, 566, 540, 482 (cm-1); HRMS (ESI-TOF) calcd for C18H15O4 [M + H]+ 295.0970, found 295.0971. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | 2?Fluoro?6?trifluoronieth 1?benz lI?urea (60 g) and 2,2.6?trimethyl?4H? 1,3? dto\tn-4-o e (4 0 g) in to uc l 00 mL ssa i etluw d br 2 h o thN mivtiuc is ad Ld p?toluene sultonic actd (7.0 and again refiuxed for h. Toluene was removed under reduced pressure and crude residue obtained was stirred for 2h in [PA (50 mL). Solidmaterial obtained was tfltered. washed with IPA and then dried to give l-(2?fiuoro?6? (it ilium omLths Mt ni?s 5?5 meth bps mi idine 2 4(1 11 3 H ?dmone ( 6 60 gL000eS\ solm ITj \MR (400 MI Ti DMSQ?d5 ) h IT 2 (s [H) 7 (m 311) 5 ?6 (s111) 21 t? 211) 4 aa (hrs flO 2 19 ( 3i1 MS 1032 M HJ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30 mg | Stage #1: 4-cyclopropylaniline; ethyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3,5-difluorophenyl)propanimidate In toluene at 100℃; for 16h; Stage #2: 2,2,6-trimethyl-4H-1,3-dioxin-4-one In toluene at 100℃; for 16h; | tert-Butyl (S)-(l-(l-(4-cyclopropylphenyl)-4-methyl-6-oxo-l,6-dihydropyrimidin-2-yl)-2- (3,5-difluorop e (Int MPlOc) To a solution of ethyl (S)-2-((tert-butoxycarbonyl)amino)-3-(3,5- difluorophenyl)propanimidate (Int MP 10b, 500 mg, 1.52 mmol) in toluene (8 mL) was added 4-cyclopropylaniline (203 mg, 1.52 mmol) and the resulting mixture was heated at 100 °C for 16 h. Mixture was then cooled to room temp, 2,2,6-trimethyl-4H-l,3-dioxin-4- one (649 mg, 4.57 mmol) was added and the mixture was heated at 100 °C for another 16 h. Mixture was then cooled, concentrated and purified by Biotage (5-70% EtOAc/hexane) to afford the title compound (30 mg). NMR (400 MHz, CDCb) δ 7.35 - 7.30 (m, 1H), 7.25 - 7.18 (m, 1H), 7.15 - 7.04 (m, 1H), 6.81 (br d, J=7.8 Hz, 1H), 6.74 - 6.62 (m, 2H), 6.27 (br d, J=6.3 Hz, 2H), 5.93 - 5.74 (m, 1H), 4.76 - 4.66 (m, 1H), 2.95 (dd, J=13.6, 5.0 Hz, 1H), 2.76 (br dd, J=13.3, 8.8 Hz, 1H), 2.40 (s, 3H), 2.05 - 1.97 (m, 1H), 1.38 (s, 9H), 1.12 - 1.06 (m, 2H), 0.85 - 0.75 (m, 2H). LC/MS: m/z = 482.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
103.5 mg | A solution of ethyl (R)-2-hydroxypropanoate (5 g, 42.3 mmol) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one (6 g, 42.3 mmol) was stirred for 4 hours at 120 C. The mixture was concentrated under vacuum to give desired product (9 g, crude) as yellow oil, which was used in the next step without further purification. ESI MS m/z=203.25 [M+H]+. Step 1-1b. A solution of the compound from step 1-1a (5 g, 24.5 mmol), 2-chloro-4-fluorobenzaldehyde (4.3 g, 27.3 mmol), TsOH (cat) and HOAc (cat) in toluene (60 mL) was stirred at 110 C. overnight. The mixture was concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired product (5.93g, 70.0%) as yellow solid. ESI MS m/z=343.00 [M+H]+. Step 1-1c. A solution of the compound from step 1-1b (5 g, 14.6 mmol), thiazole-2-carboximidamide HCl salt (2.38 g, 14.6 mmol) and K2CO3 (2.01 g, 14.6 mmol) in DMF (20 mL) was stirred for 2 hours at 80 C. It was diluted with EtOAc and washed with brine, filtered and concentrated. After the residue was purified by silica gel column (ethyl acetate/petroleum ether), the mixture was recrystallized from EtOH at 0 C. to give the desired product as yellow solid (1.25 g, 25.0%). ESI MS m/z=452.05 [M+H]+. Step 1-1d. A solution of the compound from step 1-1c (950 mg, 2.10 mmol), (Boc)2O (915.6 mg, 4.20 mmol) and DMAP (307 mg, 2.51 mmol) in DCM (30 mL) was stirred for 1 hour at rt. (0160) The reaction mixture was concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired compound as yellow solid (1.07 g, 92%). ESI MS m/z=552.30 [M+H]+. Step 1-1e. A solution of the compound from step 1-1d (965 mg, 1.75 mmol) in a solution of NaOH [40 mL, 2M in H2O/MeOH (1:5)] was stirred for 18 hours at rt. After being acidified with aq HCl (4N) to pH 5, the mixture was extracted with DCM. The organic layer was washed with aq. NH4Cl and H2O, dried (Na2SO4) and concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired compound as yellow solid (620 mg, 78%). ESI MS m/z=452.15 [M+H]+. Step 1-1f. A solution of the compound from step 1-1e (250 mg, 0.55 mmol) in DCM (10 mL) was treated with NBS (295 mg, 1.66 mmol) for 6 hours at rt. The reaction was quenched by the addition of water (2 mL) and extracted with DCM. The organic layer was dried (Na2SO4), concentrated. The residue was chromatographed (Cis column, MeCN/H2O) to give the title compound as yellow solid (103.5 mg, 33%). ESI MS m/z=566.10, 568.10 [M+H]+. 1H NMR (400 MHz, DMSO-d6) delta 8.04 (m, 2H), 7.98 (d, 1H), 7.57 (m, 1H), 7.23 (m, 1H), 6.35 (s, 1H), 4.45 (m, 2H), 1.15 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 6h; | General procedure: A solution of the appropriate alcohol, 5a-d, (25 mmol) and TMD (3.5 g, 25 mmol) in 10 ml xylene was heated under reflux in an oil bathat 150 C, for 6 h. The reaction mixture was cooled and then xylene wasremoved under reduced pressure to yield products, 6a-d which were ina high level of purity and were used immediately in subsequent reactions.34 6a, a yellow oil, with bp 183-185 C, (Lit. bp 185-187 C), 6b, ayellow oil, with bp 200-201 C, (Lit. bp 204-205 C), 6c, a yellow oil,with bp 115-117 C, (Lit bp 120-122 C) and 6d, a yellow oil, with bp270-271 C, (Lit bp 275-276 C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | In 5,5-dimethyl-1,3-cyclohexadiene Reflux; | 3.1. Synthesis General procedure: The synthetic routes for the target compounds A1-A8 and B1-B8 are depicted in Scheme 1 andthe structures are presented in Table 1. Compound 1-((2-methylthiazol-4-yl) amino) pentane-2,4-dionewas synthesized by the reaction of the commercially available 2-methylthiazol-4-amine with2,2,6-trimethyl-4H-1,3-dioxin-4-one in xylene under reflux condition. According to Scheme 1, the finalproducts were synthesized by treatment of obtained intermediate with 1,3-cyclohexadione and dierentappropriate arylaldehydes in the presence of excess amounts of ammonium acetate in reuxing ethanol.In order to synthesis the tetrahydroquinoline derivatives; the corresponding hexahydroquinolinecompound was oxidized in the presence of MnO2 in ethanol under reflux condition for 24-48 h. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 110℃;Microwave irradiation; | General procedure: 2,2,6-Trimethyl-4H-1,3-dioxin-4-one (1.1 equiv) was added to a solu-tion of aniline 7 (1 equiv) in toluene and the mixture was reacted un-der microwave irradiation (110 C, max 200 W, max 300 psi). After1.5-2 h, the solvent was removed under reduced pressure. p-ABSA(1.5 equiv) was added followed by anhydrous MeCN and the solutionwas cooled to 0 C. Et 3 N (1.2 equiv) was added dropwise over 5-10min and the mixture was stirred at RT under an N 2 atmosphere. After4 h, the solvent was removed under reduced pressure and the cruderesidue was purified by flash column chromatography to yield com-pounds 13a-g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate In tetrahydrofuran for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate In tetrahydrofuran for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In toluene Reflux; | 1.1; 3.1-6.1 (1) Preparation of chiral catalyst 2,2,6-Trimethyl-1,3-dioxin-4-one (142.2mg, 1mmol) was added dropwise to (S)-α-hydroxy-N-methyl-2-phenylacetamide ( 165.1 mg, 1 mmol) in toluene (0.5 mL). After stirring and refluxing overnight, the reaction mixture was cooled to 50°C and the solvent was removed in vacuo. The crude product was purified by silica gel column chromatography (the volume ratio of n-hexane: ethyl acetate was 20:1) to obtain 187.0 mg of white solid compound a with a yield of 75%. |
75% | In toluene Reflux; | 1.1 2,2,6-Trimethyl-1,3-dioxin-4-one (142.2mg, 1mmol) was added dropwise to (S)-α-hydroxy-N-methyl-2-phenylacetamide ( 165.1 mg, 1 mmol) in toluene (0.5 mL).After stirring and refluxing overnight, the reaction mixture was cooled to 50°C and the solvent was removed in vacuo.The crude product was purified by silica gel column chromatography (the volume ratio of n-hexane: ethyl acetate was 20:1) to obtain 187.0 mg of white solid compound a with a yield of 75%. |
75% | In toluene Reflux; | 1.1; 3.1; 4.1; 5.1 (1) Preparation of chiral catalyst I: 2,2,6-Trimethyl-1,3-dioxin-4-one (142.2mg, 1mmol) was added dropwise to (S)-α-hydroxy-N-methyl-2-phenylacetamide ( 165.1mg, 1mmol) in toluene (0.5mL) solution. After stirring and refluxing overnight, the reaction mixture was cooled to 50°C, and the solvent was removed in vacuo. The crude product was purified by silica gel column chromatography (the volume ratio of n-hexane: ethyl acetate was 20:1) to obtain 187.0 mg of white solid compound with a yield of 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
103.5 mg | Stage #1: (R)-Ethyl lactate; 2,2,6-trimethyl-4H-1,3-dioxin-4-one at 120℃; for 4h; Stage #2: 2-chloro-4-fluorobenzaldehyde With toluene-4-sulfonic acid; acetic acid In toluene at 110℃; Stage #3: 1,3-thiazole-2-carboximidamide hydrochloride; di-<i>tert</i>-butyl dicarbonate Further stages; | 1-1a; 1-1b; 1-1c; 1-1d; 1-1e; 1-1f Intermediate 1 Step 1-1a. A solution of ethyl (R)-2-hydroxypropanoate (5 g, 42.3 mmol) and 2,2,6- trimethyl-4H-1,3-dioxin-4-one (6 g, 42.3 mmol) was stirred for 4 hours at 120. The mixture was concentrated under vacuum to give desired product (9 g, crude) as yellow oil, which was used in the next step without further purification. ESI MS m/z = 203.25 (0230) [M+H]+. Step 1-1b. A solution of the compound from step 1-1a (5 g, 24.5 mmol), 2-chloro-4- fluorobenzaldehyde (4.3 g, 27.3 mmol), TsOH (cat) and HOAc (cat) in toluene (60 mL) was stirred at 110 oC overnight. The mixture was concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired product (5.93g, 70.0%) as yellow solid. ESI MS m/z = 343.00 [M+H]+. (0231) Step 1-1c. A solution of the compound from step 1-1b (5 g, 14.6 mmol), thiazole-2- carboximidamide HCl salt (2.38 g, 14.6 mmol) and K2CO3 (2.01 g, 14.6 mmol) in DMF (20 mL) was stirred for 2 hours at 80 oC. It was diluted with EtOAc and washed with brine, filtered and concentrated. After the residue was purified by silica gel column (ethyl acetate/petroleum ether), the mixture was recrystallized from EtOH at 0 oC to give the desired product as yellow solid (1.25 g, 25.0%). ESI MS m/z = 452.05 [M+H]+. (0232) Step 1-1d. A solution of the compound from step 1-1c (950 mg, 2.10 mmol), (Boc)2O (915.6 mg, 4.20 mmol) and DMAP (307 mg, 2.51 mmol) in DCM (30 mL) was stirred for 1 hour at rt. The reaction mixture was concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired compound as a yellow solid (1.07 g, 92%). ESI MS m/z = 552.30 [M+H]+. (0233) Step 1-1e. A solution of the compound from step 1-1d (965 mg, 1.75 mmol) in a solution of NaOH [40 mL, 2M in H2O/MeOH (1:5)] was stirred for 18 hours at rt. After being acidified with aq HCl (4N) to pH 5, the mixture was extracted with DCM. The organic layer was washed with aq. NH4Cl and H2O, dried (Na2SO4) and concentrated. The residue was chromatographed (silica, ethyl acetate/petroleum ether) to give the desired compound as yellow solid (620 mg, 78%). ESI MS m/z = 452.15 [M+H]+. (0234) Step 1-1f. A solution of the compound from step 1-1e (250 mg, 0.55 mmol) in DCM (10 mL) was treated with NBS (295 mg, 1.66 mmol) for 6 hours at rt. The reaction was quenched by the addition of water (2 mL) and extracted with DCM. The organic layer was dried (Na2SO4), concentrated. The residue was chromatographed (C18 column, (0235) MeCN/H2O) to give the title compound as yellow solid (103.5 mg, 33%). ESI MS m/z = 566.10, 568.10 [M+H]+.1H NMR (400 MHz, DMSO-d6) d 8.04 (m, 2H), 7.98 (d, 1H), 7.57 (m, 1H), 7.23 (m, 1H), 6.35 (s, 1H), 4.45 (m, 2H), 1.15 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In toluene Reflux; | 1.1; 6.1; 7.1; 8.1; 9.1; 10.1 (1) Preparation of chiral catalyst I: 2,2,6-trimethyl-1,3-dioxin-4-one (142.2mg, 1mmol) was added dropwise to (S)-α-hydroxy-N-methyl-2-phenylacetamide ( 165.1mg, 1mmol) in toluene (0.5mL) solution. After stirring and refluxing overnight, the reaction mixture was cooled to 50°C and the solvent was removed in vacuo. The crude product was purified by silica gel column chromatography (the volume ratio of n-hexane: ethyl acetate was 20:1) to obtain 187.0 mg of white solid compound with a yield of 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In para-xylene at 150℃; Sealed tube; Microwave irradiation; |
Tags: 5394-63-8 synthesis path| 5394-63-8 SDS| 5394-63-8 COA| 5394-63-8 purity| 5394-63-8 application| 5394-63-8 NMR| 5394-63-8 COA| 5394-63-8 structure
[ 85920-63-4 ]
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P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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